Electrocatalytic Oxidative Transformation of Organic Acids ...
How to Interpret a Great Plains Laboratory Organic Acids Test...Introduction to the Organic Acids...
Transcript of How to Interpret a Great Plains Laboratory Organic Acids Test...Introduction to the Organic Acids...
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How to Interpret a Great Plains Laboratory Organic Acids Test
Kurt N. Woeller, D.O.
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Copyright© Educational Resource Association. This material may not be reprinted, distributed or used without permission.
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Introduction to the Organic Acids Test (OAT)
The OAT for yeast & mold toxin assessment
The OAT for clostridia & other bacteria toxin assessment.
The OAT for oxalate assessment
Neurotransmitter imbalances and mitochondrial function assessment.
Indicators of other problems: nutrient deficiencies, fatty acid metabolites, etc.
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The OAT can be a complicated test with many markers indicating a variety of potential problems.
This lecture presentation focuses on what is seen most commonly in practice with regards to the OAT.
The vast majority of OAT’s (approximately 80%) that you will see from a variety of patients/clients will have similar patterns.
Each OAT needs to be applied clinically to the patient/client and treatment not just implemented based on test markers.
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Organic acids are compounds with acidic properties:◦ Carboxyl (-COOH)
◦ Alcohol (-OH)
◦ Thiol (-SH)
An accurate assessment of what is going on metabolically in the body.
Evaluates over 70 urinary metabolites that can be useful for discovering underlying causes of chronic illness.
Treatment based on OAT findings often leads to improved energy, sleep and mental health conditions, as well as reduced attention and concentration problems, chronic pain and digestive problems.
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Yeast and Fungal Markers:◦ Evaluates for invasive candida and mold toxicity
Bacterial Markers:◦ Evaluates for dysbiosis
Clostridia Bacteria Markers:◦ Evaluates for various clostridia bacteria toxins
Oxalate Metabolites:◦ Evaluates for oxalic acid toxicity and endogenous oxalate
production problems.
Glycolytic and Mitochondrial Markers:◦ Evaluates for mitochondrial dysfunction
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Phenylalanine and Tyrosine Metabolites:◦ Evaluates for phenylalanine and tyrosine metabolism which
can lead to dopamine and norepinephrine imbalances.
Tryptophan Metabolites:◦ Evaluates for issues in tryptophan metabolism which
contributes to serotonin imbalance and excess quinolinic acid production.
Pyrimidine Metabolites:◦ Evaluates for uracil and thymine as indicators of folate
imbalance.
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Ketone and Fatty Acid Oxidation:◦ Evaluates for fatty acid metabolism problems which can
contribute to mitochondrial dysfunction.
Nutritional Markers:◦ Evaluates for various nutrient imbalances
Indicators of Detoxification:◦ Measures organic acids linked to glutathione status
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Amino Acid Metabolites:◦ Measures organic acids linked to inborn errors of metabolism
and other metabolic imbalances.
Mineral Metabolism:◦ Measures phosphoric acid linked dietary consumption of
phosphate (processed foods), as well as bone metabolism and vitamin D status.
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Autism
ADD/ADHD
Autoimmune
Chronic fatigue
Digestive problems
Metabolic disorders
Mental health disorders
Neurological disorders
Any individual with a chronic health
condition where you suspect metabolic
toxins may be a causative or
contributing factor.
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Suggestions For Reviewing An
Organic Acids Test
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Page 1 – Yeast and Fungal Markers
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Page 1 – Bacterial and Clostridia Markers
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Page 2 - Oxalate and Mitochondrial Metabolites
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Page 2 – Neurotransmitter Metabolites
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Page 3 – Pyrimidines and Fatty Acids
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Page 3 – Nutritional Markers
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Page 4 – Indicators of Detoxification
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Page 4 – Amino Acid Metabolites and Phosphoric Acid
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François L. Mayer, et. Al. Candida albicanspathogenicity mechanisms. Virulence. Feb
15, 2013; 4(2): 119–128.
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Candida invasion into tissue
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Inhibited by Tartaric Acid & Citramalic Acid
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Shaw, W Increased Urinary Excretion of Analogs of Krebs Cycle Metabolites and Arabinose in Two Brothers with Autistic
Features. Clin Chem 41:1094-1104, 1995
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Shaw, W Increased Urinary Excretion of Analogs of Krebs Cycle Metabolites and Arabinose in Two Brothers with Autistic
Features. Clin Chem 41:1094-1104, 1995
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0.00
500.00
1000.00
1500.00
2000.00
2500.00
3000.00
3500.00
4000.00
N = 14
N = 30
N = 211
CONTROLMALE
INFANTS
CONTROLMALE
CHILDREN
AUTISTICMALES
AR
AB
INO
SE
(MM
OL
/MO
L C
RE
AT
ININ
E)
2 - 13 YRS
2 - 13 YRS
P<.005
Shaw, W., et al Assessment of antifungal drug therapy in autism by measurement of suspected microbial metabolites in urine withGC/MS. Clinical Practice of Alternative Medicine: 15-26,2000
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Intestine
Y = yeast
* = yeast product
Blood vessel
Rest of body
Kidney
urinecup
Y * B
Y
Normal Intestine
*
*
*
*
*
BBB
BB
B BB BB
B
B
B B
BB
B B BB
B B
B
B
B BB
B= good bacteria
=bad bacteria29
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Intestine
Y
Y = yeast
YY
Y
Y
Y
*Y
Y
Y
* = yeast product
* *
**
***
***
***
*
*
****
*******
Blood vessel
*
*
*
*
Rest of body
*******
**
****** **
***
*****
** * * ****
urinecup
Kidney
*
* B*
**
*
***
***
* B
***************
**********
After Antibiotics
B= good bacteria
**** *
* * *
* *
= bad bacteria
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Schizophrenia
Alzheimer’s disease
Systemic lupus erythematosus (SLE)
Fibromyalgia
Chronic fatigue syndrome & CFIDS
HIV infection
Colitis Depression PMS Vaginal yeast
infection Multiple sclerosis Interstitial cystitis Seizures Irritable bowel Cancer
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SCORE:
0 = none1 = occasional or mild2 = frequent or moderately severe3 = severe or disabling
1. Have you, at any time in your life, taken broad spectrum antibiotics? (0 or 3)2. Have you taken tetracycline or other broad-spectrum antibiotics for
one month or longer? (0 or 3)3. Are your symptoms worse on damp, muggy days or in moldy places? (0 or 3)4. Do you crave sugar? (0 or 3)5. Do you have a feeling of being "drained?” (0, 1, 2 or 3)6. WOMEN: Are you bothered with vaginal burning, itching or discharge? (0, 1, 2 or 3)
MEN: Do you have burning, itching or discharge from the penis? (0, 1, 2 or 3)7. Are you bothered by burning, itching or tearing of your eyes? (0, 1, 2 or 3)
TOTAL SCORE FOR FRDQ-7:
Score 0-3 = FRD unlikelyScore 4-9 = FRD probableScore 10-21 = FRD almost certain
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The Centers for Disease Control estimates that there were 453,000 documented cases of Clostridium difficile infection (CDI) in the United States in 2011 leading to 29,300 deaths.
Between 10% and 30% of people who have an initial episode of CDI will develop at least one recurrence.
On the basis of the number of incident cases found in 2011, 45,300-135,900 people developed recurrent CDI.
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Toxin A Toxin B
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These two toxins are the main virulence factors related to mucosal damage from C. difficile.
Toxins A & B lead to digestive tract inflammation, e.g. Pseudomembranous colitis or clostridia difficile associated diarrhea (CDAD).
Toxin A & Toxin B are both capable of causing mucosal damage (Kuehne SA, Cartman ST, Heap JT, Kelly
ML, Cockayne A, Minton NP; October 2010. "The role of toxin A and toxin B in Clostridium difficile infection". Nature 467 (7316): 711–3).
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Structure of 3-(3-hydroxyphenyl)-3-hydroxypropionic acid
HO
CHOHCH2COOH123
1
23
4
5 6
Phenyl group
Hydroxyl group
Propionic acid
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Structure of 4-cresol (methylphenol)
HOCH31
2
3
4
5 6
Phenyl group
Hydroxyl group
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Distribution of values for HPHPA Clostridia metabolite in urine samples of male infants,
control boys, and boys with autism
Controlinfants
Control boys2-13 years
Autistic Boys2-13 years
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Nutritional Neuroscience 2010 Vol 13 No 3: 1-10
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Acute Schizophrenia
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Organic Acids Test
Organic Acids Test
Organic Acids Test
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Homovanillic acid (HVA)Dihydroxyphenylacetic(DOPAC)
Cycled thousands of times
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Fig. 2. The tricarboxylic acid cycle during high levels of propionic acid. Propionic acid, presumably derived from Clostridia spp., is metabolized to propionyl-CoA using acetyl-CoA. Propionyl-CoA is further metabolized into methylmalonyl-CoA, which enters the tricarboxylic acid cycle as succinyl-CoA. Succinyl-CoA inhibits the first and fourth enzyme in the tricarboxylic acid cycle. In this manner, propionic acid may ‘short circuit’ the
tricarboxylic acid cycle, thereby reducing the production of nicotinamide adenine dinucleotide (NADH). This decrease in NADH is hypothesized to cause the decrease in complex I activity measured in the patients with
consistent elevations in short and long acyl-carnitines (CESLAC)
From: Gastrointestinal dysfunction in autism spectrum disorders: the role of the mitochondria and the enteric microbiome (2015).
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75-90% of kidney stones are oxalates. 10-15 percent of adults will be diagnosed with a kidney stone in their lifetime.
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GlyoxylateGlycerate
Glycolatehydroxypyruvate
GRHPRGlyoxylate reductaseHydroxypyruvic reductaseType II Hyperoxaluria
GlycolateOxidase (GO)
B-6Glycine
LDHLactatedehydrogenase
Oxalate AscorbateArabinose
YeastFungi
AGTAlanineGlyoxylateAminoTransferaseType IHyperoxaluria
Oxalates diet
dietEthylene glycol
Oxalate Metabolism
hydroxyproline
Protein,Gelatin
Protein
Collagen
Candidacollagenase
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Arthritis
Behavior problems in children
Interstitial cystitis
Joint pain
Fibromyalgia
Heart disease (atherosclerosis, conduction issues)
Heavy metal toxicity
Osteoporosis
Thyroid problems
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Quinolinic AcidProduction
Serotonin
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Oxidized Reduced
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Redox Reactions
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Serotonin
Quinolinic acid
GammaInterferonfrom immune system due toinfection
Kills cells containing bacteria, viruses, parasites. May also damage infectious organisms themselves. IDO causes drastic reduction in
tryptophan for protein synthesis needed by infected cells and infectious organisms - tryptophan at very low levels.
Beta amyloid peptide-Alzheimer’s
Excess tryptophanCauses failure toKill infectious agents
CortisolStress
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Amyloid fibrils propagate from yeast surfaces and capture Candida
albicans in culture medium.Credit: D.K.V. Kumar et al. / Science
Translational Medicine (2016)
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Bisphenol A
OxybenzoneFlouride
Parabens
Phthalates
Butylated Hydroxyanisole (BHA)
Perfluorooctanoic Acid (PFOA)
Perchlorate
Decabromodiphenyl Ether (DECA)
Asbestos
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Quinolinic AcidProductionSerotonin
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Glutathione Deficiency
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Isoleucine-branched chain amino acid
2-oxo-3-methylvalerate
2-methylbutyryl CoA
tiglyl-CoA tiglylglycine
2-methyl-3-hydroxybutyryl-CoA
2-methylacetoacetyl-CoA
NAD+
NADH
MitochondrialRespiratory Chain-Complex I
Acetyl CoA
2-MAA Thiolase
MHB-CoADehydrogenase
+ Propionyl CoAMethylmalonyl CoA
Succinyl CoA
2-methyl-3-hydroxy-butyric acid
Tiglylglycine as a marker of
mitochondrial dysfunction
2-methylbutyrylglycine
Associated with autism
x
Measured in popular TOX test
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General supplement support and antioxidant therapy can be helpful for mitochondrial issues.Examples:
• L-Carnitine – helps with fatty acid transport
• CoQ10 (Ubiquinol)
• Thiamine (B1), Pyridoxine (B6), Riboflavin (B2) - all support mitochondrial function.
• Antioxidants – help to decrease oxidative stress
• ‘Mitochondrial Cocktail’ – combination approach for balanced mitochondrial support, e.g. CoQ10, NADH.
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X
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X
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Beta-oxidation is the process by which fatty acid are broken down in the mitochondria to generate acetyl-CoA. The acetyl-CoA then enters citric acid cycle generating NADH which is used by the electron transport chain.
#44 - #48 are specific indicators ofoxidation of fatty acids in the cytoplasm of the cell:• Fatty acid oxidation disorders• Carnitine deficiency• Fasting • Large intake of Medium Chain
Triglycerides, i.e. baby formulas• Supplementation of 500mg to
1000mg of L-Carnitine may be beneficial.
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2 year old girl from China
High Dose Medium Chain Triglycerides (MCT Oil)
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Indirect: Methylmalonic acid - vitamin B-12 Methylcitric acid - biotin Glutaric and 3-hydroxy-3-methylglutaric - indicators of
riboflavin and coenzyme Q-10 deficiency, respectively.
Direct: Ascorbic acid - vitamin C Pantothenic acid - B vitamin Pyridoxic acid - metabolite of vitamin B-6
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Elevated in cancer, genetic disease,
folate issuesPyrimidines
Pyrimidines
Uracil
Thymine
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High values
• High intake
• Hyperparathyroidism
• Vitamin D-resistant rickets
• Immobilization following paraplegia or fracture
• Vitamin D intoxication
• Renal tubular damage, heavy metal toxicity
• Familial hypophosphatemia
• Metabolic acidosis
Low values
• Low intake
• Hypoparathyroidism
• Pseudohypoparathyroidism
• Parathyroidectomy
• Vitamin D deficiency
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Phosphoric Acid
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Phosphoric Acid
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2-Hydroxyhippuric
2-Hydroxyhippuric
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Structure of 2-Hydroxyhippuric Acid - metabolite of aspartame (Nutrasweet®), aspirin, foods, additives
HO
CONHCH2COOH1
2
3
4
5 6
Phenyl group
Hydroxyl groupglycine
Salicylate94
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Structure of Aminophenol –major acetaminophen metabolite
HO1
2
3
4
5 6
Phenyl group
Hydroxyl group
NH2
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Structure of 4-cresol (methylphenol)
HOCH31
2
3
4
5 6
Phenyl group
Hydroxyl group
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Potential Sources of Stress
Clinical Conditions
Chronic viral infections (EBV,CMV,Herpes I-II,etc.)Increased infectionsYeast overgrowthAllergiesFatigueHeadachesAutoimmune diseaseCancerCardiovascular disease
InsomniaHypoglycemiaHungerPMSDepressionIrritable bowelDigestive problemsADD/ADHD
Sympathetic System
HP
Stressor
Epinephrine
NE
NFL
Adrenal Cortex
TotalDHEA(s)
FreeDHEA(s)
ACTH
TotalCortisol
Free
Cortisol
Elevated Cortisolto DHEA Ratio*
Reduced HP Sensitivity to Negative Feedback
Energy Production• Insulin sensitivity• Glucose utilization• Blood sugar• Gluconeogenesis
Other Influences• Osteoporosis (bone loss) • Fat accumulation (waist)• Protein breakdown• Salt & water retention
Immune Activity• Secretory IgA• Antigen penetration • Circulating IgG• NK cell activity• Interleukin 2• T-Lymphocytes
KEYAssociationStimulusOutcomeInhibitionHP = Hypothalamus - PituitaryNFL = Negative Feedback LoopNE = Norepinephrine
* Abnormal Ratio ofCortisol to DHEA indicates
Pregnenolone Steal (Cortisol Escape)
Anger - FearWorry/Anxiety
DepressionGuilt
OverworkPhysical and Mental strain
Excessive exerciseSleep deprivation
Light-cycle disruptionLate hours
SurgeryTrauma/Injury
Whiplash – Head injuryInflammation
PainTemperature extremes
Toxic exposureInfections
Chemicals - Heavy metalsElectromagnetic fields
RadiationGeophysical
MalabsorptionMaldigestion
IllnessLow blood sugar - Poor diet
Nutritional deficienciesAllergiesFoods
Mold – Pollens
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